INFLUENCE OF THE RENAL SYMPATHETIC-NERVES ON RENAL RENIN AND ANGIOTENSINOGEN GENE-EXPRESSION IN SPONTANEOUSLY HYPERTENSIVE RATS DURING DEVELOPMENT

Objective: To investigate the influence of renal sympathetic denervation on renin and angiotensinogen gene expression in the kidney during growth and the development of hypertension in spontaneously hypertensive rats (SHR). Comparative studies were undertaken in age-matched normotensive Wistar rats. Design: Four-week-old SHR and Wistar rats were subjected to either denervation of the left kidney or sham operation. At age 5, 7 or 9 weeks the rats were lightly anaesthetized, carotid blood pressure was measured, a blood sample was taken and both kidneys were removed. Method: Plasma renin activity was measured by radioimmunoassay, and renal renin and angiotensinogen messenger RNA (mRNA) levels were measured by Northern blot hybridization followed by densitometric analysis. Results: In 5- and 7-week-old SHR the renin mRNA level in the left kidney was significantly suppressed compared with that in the sham-operated right kidney and with the level in 9-week-old SHR. The renal renin mRNA level in sham-operated SHR decreased significantly with increasing age, whereas in the Wistar rats the renal renin mRNA level did not change at any age and was not affected by renal denervation. The renal angiotensinogen mRNA level gradually increased with age in both rat strains and was not affected by denervation, but much higher levels were attained in the Wistar rats than in the SHR. Conclusion: Renal angiotensinogen gene expression was depressed in the SHR, with little evidence of neural regulation at any age in the SHR or the Wistar rats. However, in the SHR the renal sympathetic nerves elevated renal renin gene expression in the prehypertensive stage, but their influence decreased as hypertension developed.